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Corey J Langer
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OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
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OA01.08 - Discussant - OA 01.05, OA 01.06, OA 01.07 (ID 14547)
11:45 - 12:00 | Presenting Author(s): Corey J Langer
- Abstract
- Presentation
Abstract not provided
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OA07 - Oligometastasis: What Should Be the State-Of-The-Art? (ID 905)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 107
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OA07.01 - Phase II Study of Pembrolizumab for Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Following Completion of Locally Ablative Therapy (LAT) (ID 12590)
15:15 - 15:25 | Author(s): Corey J Langer
- Abstract
- Presentation
Background
Patients (pts) with oligometastatic NSCLC may benefit from LAT (e.g., surgery, stereotactic radiation (SRT)). It is unclear if systemic therapy can provide benefit after LAT. We completed a Phase II study evaluating the efficacy of pembrolizumab after LAT, hypothesizing that immunotherapy would be effective in the setting of a minimal disease burden.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligibility stipulated oligometastatic NSCLC (up to 4 sites) with completion of LAT to all known sites of disease. Within 4-12 weeks of completing LAT, pts began pembrolizumab 200 mg every 21 days for 6 mos, with a provision to continue for up to a year in the absence of progression (PD) or toxicity. Progression-free survival (PFS) and overall survival (OS) were measured from the start of LAT. A sample size of 42 pts would provide 80% power for a test at 5% 1-sided type I error to increase PFS to >=10 mos compared to a historical control PFS of 6.6 mo.
4c3880bb027f159e801041b1021e88e8 Result
Since January 2015, 45 pts have been enrolled. Median age is 64 years; 53% male; 89% Caucasian; 89% current and former smokers. Most common metastatic sites are lung (16 pts), brain (18), liver (9), and bone (9). LAT included surgery (30 pts), SRT (30), and chemoradiotherapy (23). Adverse events have been mostly mild. There were two episodes of Grade 3 pneumonitis, two episodes of Grade 3 colitis, and one episode of Grade 3 adrenal insufficiency. Median follow-up from start of LAT is 20.1 mos. To date, 19 pts have had PD or died. Median PFS was 25 mos. PFS rates (+ SE) at 12, 18 and 24 mos are 72%+7%, 54%+9% and 50%+9%, with 10 free of PD/death beyond 24 mos. To date, 10 pts have died. Median OS has not yet been reached. OS rates (+ SE) at 12, 18 and 24 mos are 91%+4%, 82%+7% and 73%+8%, with 14 pts alive beyond 24 mos. Median PFS was 16.9 mos for pts with metachronous disease (n=33), not yet reached for pts with synchronous disease (n=12). Median OS has not yet been reached in either group.
8eea62084ca7e541d918e823422bd82e Conclusion
Pembrolizumab after LAT for oligometastatic NSCLC is feasible and well tolerated. PFS appears quite favorable, preliminarily Final analysis will be performed September 2018. Updated survival estimates and biomarker data will be presented.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-64 - Impact of STK11 Co-Mutation on Outcomes Following Immunotherapy Among Patients with TP53 and KRAS Mutated Stage IV NSCLC (ID 12581)
16:45 - 18:00 | Author(s): Corey J Langer
- Abstract
Background
Mutations in LKB1/STK11 may predict a poor response to immunotherapy in NSCLC. We previously showed that pretreatment neutrophil-to-lymphocyte ratio (NLR) >5 predicted a poor response to immunotherapy in NSCLC. We evaluated the impact of STK11 mutation (MT) alone, and co-existing MTs in KRAS and TP53 on outcomes in patients (pts) treated with immunotherapy at the University of Pennsylvania. The role of NLR was also evaluated.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with metastatic NSCLC that underwent NGS and who received 2nd-line immunotherapy were identified (2/2013 – 12/2016). Patient demographics, tumor characteristics, and outcomes were analyzed from the electronic medical record. Chi-square and the Wilcoxon Rank-Sum test were used to assess correlation between NLR and MT status. Median overall survival (mOS) and median progression free survival (mPFS) times are estimated from Kaplan-Meier curves. A Cox proportional hazard model (HR) was used to assess the effect of mutation status on survival outcomes.
4c3880bb027f159e801041b1021e88e8 Result
110 pts were included with the following MT status: 5 STK11, 16 KRAS, 29 TP53, 13 KRAS/TP53, 7 KRAS/STK11, 9 TP53/STK11, 7 KRAS/TP53/STK11, 24 no STK11, KRAS or TP53 MT. In univariate and multivariable analyses, STK11 MT was not independently associated with mPFS or mOS after immunotherapy. Among pts with TP53 MT, the presence of a STK11 MT was associated with improved mPFS (4.3 vs. 2 mo, HR 0.416, p=0 .035, (95% CI 0.18 –0.94)) and statistically similar mOS (13.1 vs 6.8 mo, HR 0.43, p=0.09 (95%CI 0.16–1.14)) compared with STK11 wild type (WT). Conversely, among pts with KRAS MT, the presence of a STK11 MT was associated with similar mPFS (2.2 vs 2.8 mo, HR 1.64, p=0.247 (95% CI 0.7–3.8)) and mOS (3.5 vs 7.7 mo, HR 2.3, p=0.09 (0.16–1.14)) compared with STK11 WT. NLR did not correlate with MT status. After stratifying for NLR (<5 and >5), the effect of STK11 MT on mOS in the TP53 MT group was amplified in pts with NLR<5 (n=46, HR 0.05, p=0.021, 95% CI 0.004-0.63) compared to TP53 MT with STK11 WT (HR 4.3, p=0.036 (95% CI 1.1-16.9)).
8eea62084ca7e541d918e823422bd82e Conclusion
STK11 mutation status alone does not correlate with pre-treatment NLR and is not independently associated with survival outcomes after immunotherapy. PFS following immunotherapy is improved in patients with co-existing TP53 and STK11 MT compared to STK11 WT. An OS benefit after immunotherapy is amplified in patients with NLR<5, TP53 MT, and STK11 co-MT.
* Authors Marmarelis and Bange contributed equally
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-42 - Impact of Tobacco Smoking on Outcomes in Patients with Metastatic Non-Small Cell Lung Cancer in the Era of Targeted Therapy (ID 13849)
16:45 - 18:00 | Author(s): Corey J Langer
- Abstract
Background
Prior epidemiological studies have noted differences in the demographic and clinical characteristics among patients with metastatic non-small cell lung cancer (NSCLC) between those with and without exposure to tobacco smoke. Most notably never smokers are more likely to harbor genomic driver mutations and (in the era of targeted therapy) improved survival. Observational databases, capturing real world diagnostic and treatment patterns, can provide insights on outcomes of NSCLC based on smoking history.
a9ded1e5ce5d75814730bb4caaf49419 Method
The electronic health records (EHR) of patients with de novo stage IV NSCLC diagnosed between January 2013 and December 2016 from 30 cancer centers, contributing to the Cota Observational Cancer Database, from 184 oncologists were reviewed.
4c3880bb027f159e801041b1021e88e8 Result
1716 NSCLC pts were identified including 243 (14.2%) never tobacco smokers, 405 (23.6%) active smokers, 1026 (59.8%) former smokers, 7 (0.4%) passive smokers, and 29 (1.7%) not reporting. Never Smokers (NS) were more likely than smokers (S=active and former smokers combined) to be female (NS: 67.4%; S: 47.2%; p<0.0001) with similar ages (NS: 66 yrs; S: 67 yrs), but included more Asians pts (7.4% vs 1%, p<0.0001). Histologic subtypes differed: Squamous NS: 9%; S: 17.8%: (p<0.0001), AdenoCA NS: 73.2%; S: 68% (p=0.1), NOS N: 5.3%; S: 6.1% (p=0.8). Genomic profiling for EGFR/ALK was more common and identified more mutations in the NS cohort. In the non-squamous histologies EGFR testing was NS: 87% with 45.9% mutated; S: 70% with 10.4% mutated (tested p<0.0001; mutated p<0.0001). In the non-squamous histologies ALK testing was NS: 74% with 5.4% translocated ; S: 67% with 1.4% translocated (tested p=0.04; translocated p<0.001). As first line therapy 40% of NS received targeted therapy (11% receiving targeted 2nd line) whereas 4.8% S received 1st line and 1.5% 2nd line targeted therapy. The median overall survival for the NS cohort was 21 months compared to 11 months among S (log-rank p<0.05); with PFS of 9 vs 6 months (p<0.05). Excluding use of targeted therapy in 1st or 2nd line, the median OS for NS was 17 mo; for S was 10 mo (p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
This real world observational study confirms a higher rate of targetable genomic driver mutations among never smoker NSCLC. Despite guidelines recommending universal genomic testing, never smokers are tested at a higher frequency. In the era of targeted therapy (but before the widespread use of immunotherapy) never smoker NSCLC patients experienced improved overall survival with and without targeted treatment compared to individuals with tobacco exposure.
6f8b794f3246b0c1e1780bb4d4d5dc53
